The present invention relates to the transdermal application of deuterated drugs. Although the transdermal application of drugs undoubtedly has great advantages, there is the disadvantage that the amount of drug that can be absorbed via the skin is limited. Thus, when the therapy by dermal application began, attempts were made at the same time to find a way of increasing the capacity of drugs to penetrate through the skin. The development of penetration enhancers which are added to drugs for dermal application was regarded as a solution for this problem first. These substances change subjacent skin structures, at least for a short time, and can result in undesired side effects in unfavorable cases. Other possibilities of increasing the absorption of active substances is to remove the stratum corneum by a laser treatment or by repeated sticking and tearing-off adhesive strips, the so-called "stripping". The drawback of this method is the fact that not only the desired penetration of the active substance into the human body is facilitated but also that of all other substances as well as of micro-organisms, such as bacteria and fungus spores. Another way of improving the dermal absorption is to use current. As is known to medical experts, this process, known under the term "iontophoresis", cannot be applied without pain. The same applies to the so-called "spiked patch". This administration form is fixed to the body by means of cannulae penetrating the horny layer of the skin. The active substance release takes place through said cannulae which simultaneously serve as fixation aids.
The dermal application of so-called "pro-drugs" seems at first to be an interesting alternative. In this case structural elements of drugs which are considered to be particularly unfavorable for the dermal absorption, e.g., phenolic hydroxyl groups, are derivatized, e.g., esterified. The characteristic feature of the chemical modification of pro-drugs is the fact that the derivatization is extremely unstable so that the drug underlying the pro-drug is quickly and completely formed in vitro. However, it is known to the skilled artisan that this actually neat idea can only rarely be realized in practice, since the intended quick and complete metabolic degradation does not take place in vivo. Thus, some toxicological questions arise with respect to the pro-drugs which still require extensive pharmacologic studies.
By way of trial, radioactively labeled drugs were applied transdermally in the past, in order to facilitate the determination of the extremely low blood levels frequently occurring after transdermal application; an exchange of radioactive components under in-vivo-conditions was not intended to take place.